This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza virus infections result in significant morbidity and mortality each year, especially in immunocompromised individuals. Despite this, the current vaccine does not result in long-term protection against serologically distinct viruses. Additionally, individuals with autoimmune disorders, such as systemic lupus erythematosus, generate reduced antibody responses following influenza vaccination and remain susceptible to infection. Therefore there is considerable interest in understanding how to generate long-lasting memory to influenza, especially in individuals with autoimmune disorders. This study utilizes three mouse models that develop spontaneous lupus-like disease to examine the susceptibility, anti-influenza response, and disease development following infection. In Aim 1, the investigator examines the ability of lupus prone mice to clear viral infection. Aim 2 will focus on the ability of these mice to mount a protective anti-influenza response composed of neutralizing antibodies and memory CD4+ and CD8+ T cells. Finally, Aim 3 examines the impact of influenza virus infection on the development of autoantibodies, autoreactive T cells, and end stage organ disease. This data will provide valuable information on how autoimmunity impacts the immune response to influenza virus and additionally will provide a model system to test novel vaccination strategies.